Itziar de Aguirre Egaña

Size: px
Start display at page:

Download "Itziar de Aguirre Egaña"

Transcription

1 Universitat Autònoma de Barcelona Facultat de Medicina PhD programme: Departamento de Medicina Interna Thesis entitled: LKB1/ AMPK / TSC2 signaling pathway alterations in Non-Small-Cell-Lung-Carcinoma Present by: Itziar de Aguirre Egaña Thesis Advisors: Director: Dr. Paula Vertino Director: Dr. Rafael Rosell i Costa Itziar de Aguirre Egaña Dr. PM Vertino Dr. Rafael Rosell Costa Badalona, 2014

2 Paula M. Vertino, Professor at the Department of Radiation Oncology at Emory University School of Medicine and leader of Cancer Genetics and Epigenetics Program, Winship Cancer Institute of Emory University (Atlanta, Georgia). CERTIFICA Que la Tesi Doctoral titulada: LKB1/ AMPK / TSC2 signaling pathway alterations in Non-Small-Cell- Lung-Carcinoma, ha estat realitzada per la llicenciada Itziar de Aguirre Egaña sota la seva direcció, en codirecció amb el Dr. Rafael Rosell i Costa, i considera que és apta per a la seva defensa pública davant d un Tribunal per optar al grau de Doctora per la Universitat Autònoma de Barcelona. I per tal que quedi constància, signa aquest document. Dra. Paula M. Vertino Badalona, Juny 2014

3 En Rafael Rosell i Costa, Professor Associat del Departament de Medicina de la Universitat Autònoma de Barcelona i director del Cancer Biology & Precision Medicine Program de l Institut Català d Oncologia, Hospital Universitari Germans Trias i Pujol, CERTIFICA Que la Tesi Doctoral titulada: LKB1/ AMPK / TSC2 signaling pathway alterations in Non-Small-Cell- Lung-Carcinoma, ha estat realitzada per la llicenciada Itziar de Aguirre Egaña sota la seva direcció, en codirecció amb la Dra. Paula M.Vertino, i considera que és apta per a la seva defensa pública davant d un Tribunal per optar al grau de Doctora per la Universitat Autònoma de Barcelona. I per tal que quedi constància, signa aquest document. Dr. Rafael Rosell i Costa Badalona, Juny 2014

4 Acknowledgements These lines are to deserve my sincere acknowledgment to all the people who helped me to develop this work: First of all, words cannot express how grateful I feel toward my advisors, Paula M. Vertino and Rafael Rosell i Costa, each of them is a great scientist and an expert in their field. Thanks to Paula M. Vertino for her kindness providing unlimited support over the last years, without her guidance and supervision have not been able to develop this research. Also I m grateful to her to motivate me in difficult moments and for all she kindly taught me about molecular biology. A massive thank you to Rafael Rosell i Costa, for the opportunity he offered me to live my american experience. It was a very rich, an extremely useful, and a fruitful experience. Thanks to Wei Zhou, Diansheng Zhong and Michael, lovely people who always had the willingness to help with a big smile. Thanks for their generosity. I would like to thank Vertino s lab : Krithika Subramanian, Doris Powell, Melissa Pourpak, Annalisa Stoney and Mary Lucas Smith, for their help in the laboratory and the excellent time I enjoyed working and entertaining with them. You made me feel at home!!! Many thanks to Professor Xavier León Vintró, a generous person who without knowing me, he developed the statistical analysis of this thesis, at a time when it was not any exit. I m grateful to Pedro Lopez de Castro, for his contribution in the tedious and laborious step of collecting the clinical data of patients analyzed. I m grateful to Jose Luis Mate, for his cooperation from the Department of Pathology. I would also like to thank all members of the Oncology Service, Hospital Germans Trias i Pujol, they always found time to answer my queries. Last but certainly not least, I would like to express my enormous gratitude to all my family and friends for their unlimited support, unconditional encouragement and patience. It would take too long to acknowledge everyone by name, but you know who you are, to all of you ESKERRIK ASKO, MOLTES GRÀCIES, THANKS!!!

5 INDEX INDEX Page Abbreviations...IV I. Introduction Lung Cancer Epidemiology of Lung Cancer Incidence Mortality Lung cancer causes Types of Lung Cancer SCLC NSCLC Stage of lung cancer Stages of Small Cell Lung Cancer Stages of Non-Small Cell Lung Cancer Epigenetic alterations in DNA Epigenetic modifications X chromosome inactivation Genomic imprinting DNA methylation What is methylation? Distribution of methylated cytosines and CpG islands DNA methyltransferases DNA Methyation in Cancer Techniques to study DNA methylation Clinical implications of DNA methylation Methylation &Tumor suppressor genes Chromatin and Methylation Histone Acetylation/ Deacetylation Histone deacetylase and Methyl-binding domain

6 INDEX 3. Tumor suppressor genes & familial cancer Peutz Jeghers Syndrome (PJS) PJS & LKB LKB Posttranslational modifications of LKB LKB1 functions Regulation of LKB1: LKB1-STRAD-MO25 complex LKB1 & Lung Cancer LKB1/ AMPK/ TSC pathway AMP-activated protein kinase (AMPK) LKB1 activates 12 kinases of AMPK family Tuberous sclerosis complex (TSC) Rheb (Ras-homolog enriched in brain ) /mtor (target of rapamacyn), downstream effectors of LKB1/AMPK/TSC pathway II. Rationale III. Objectives IV. Material & Methods Cell Lines NSCLC Paraffin Embedded Tissues Acid Nucleic isolation from cell line Genomic DNA isolation RNA isolation Genomic DNA isolation from Paraffin Embedded Tissue DNA isolation Mutations of LKB1/AMPK/TSC Analysis of LKB1 and AMPK mutations by DNA sequencing Protein truncation analysis of TSC Bisulfite modification-msp Reverse transcription-polymerase chain reaction (RT-PCR) Quantitative PCR real-time (qrt-pcr) Reagents and 5-aza-dC and TSA treatment

7 INDEX 15. LKB1 small interfering RNA treatment Cell Lysis & Protein extraction Assessment of protein Western Blotting V. Results Genetic and Epigenetic alterations in LKB1/AMPK/TSC LKB1 activates 12 kinases of AMPK subfamily Determine the BRSK2 expression in a panel of 23 cell lines BRSK2 methylation status in paraffin embedded tumor tissues Inhibition of LKB1 Protein expression via sirna VI.Discussion Aim I. Determine the frequency of LKB1/AMPK/TSC2 signaling pathway alterations in NSCLC Aim II. Study LKB1/AMPK-related kinases alterations as an additional molecular mechanism for the development of lung cancer Aim III. Consequences of BRSK2 methylation Aim IV. Clinical validation of BRSK2 methylation status, in paraffin embedded tumor tissues of patients with lung cancer Aim V. Inhibition of LKB1 protein on NSCLC cell lines VII.Conclusions VIII. References

8 ABBREVIATIONS Abbreviations 1x TE 1 mm Tris-HCl (ph 7.5), 1 mm EDTA, sterile solution. 4EBP1 Eukaryote initiation factor 4E Binding Protein 1 5aza-Dc 5-azadeoxycytidine AC Adenocarcinoma ADP Adenosine diphosphate AJCC American Joint Committee on Cancer AKT Serine/threonine protein kinase B AMPK AMP-activated protein kinase APC Adenomatous Polyposis Coli ASC Adenosquamous ATCC American Type Culture Collection ATM Ataxia-Telangiectasia-Mutated kinase ATP Adenosine-5'-triphosphate BAC Bronchioloalveolar carcinoma bp Base pairs BRSK Brain Specific protein Kinase C Cytosine CBS domain Cystathionine β-synthase domain CH 3 Methyl group CO 2 Carbon dioxide COPD Chronic Obstructive Pulmonary Disease Cys Cysteine DECP Diethylpyrocarbonate DNA Deoxyribonucleic acid DNMT DNA-5-methyltransferase EDTA Ethylenediaminetetraacetic acid FBS Fetal bovine serum GADPH glycerradehyde 3-phophate dehydrogenase GAP GTPase- activating protein GBD Glycogen-Binding Domain

9 ABBREVIATIONS GTP Guanosine triphosphate GTPase Family of hydrolase enzymes that can bind and hydrolyze GTP HDAC Histone Deacetylase IGF1 Insulin-like growth factor1 IRS1 Insulin Receptor Substrate-1 LCC Large cell carcinoma LKB1 l LKB1 splice variant, generate a protein of 50-kDa LKB1 Serine-Threonine Protein Kinase, LKB1 s LKB1 splice variant, generate a protein of 48-kDa LOH Loss of Heterozygosity MAPK Mitogen Activated Protein Kinase MARK MAP/ microtubule affinity regulating kinase MBD Methyl Binding Domain MDR1 Multidrug resistance gene 1 MECP2 5-Methyl-cytosine binding protein MgCl2 Magnesium chloride MGMT O6-methylguanine-DNA-methyltransferase M-MLV retrotranscriptase Moloney Murine Leukemia Virus retrotranscriptase MO25 Mouse protein 25 mrna Messenger Ribonucleic Acid MSP Methylation Specific PCR mtor Mammalian Target of Rapamycin NaOH Sodium hydroxide NH4SO4 Ammmonical Nitrogen NSCLC Non Small Cell Lung Cancer PAR Partitioning defective gene family PCR Polymerase Chain Reaction PI3K phosphoinositide 3-kinase PIP3 Phosphatidylinositol 3,4,5-triphosphatase PJS Peutz-Jeghers Syndrome PKA camp-dependent protein kinase

10 ABBREVIATIONS PTEN Phosphatase and tensin homolog PTT Protein Truncation Test PVDF Polyvinylidene fluoride membrane qrt-pcr Quantitative PCR real-time RARβ Retinoic Acid Receptor β RB Retinoblastoma tumor-suppressor Rheb Ras-homolog enriched in brain RNA Ribonucleic acid RNase Ribonuclease RPMI Roswell Park Memorial Institute medium RSK p90 ribosomal S6 protein kinase RT-PCR Reverse Transcription Polymerase Chain Reaction S6K p70 ribosomal S6 kinase 1 SAD Synapses of amphids defective SAM S-adenosylmethionine SCC Squamous cell carcinoma SCLC Small Cell Lung Cancer SDS Sodium dodecyl sulfate SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis sirna Small interfering RNA STK11 Serine-Threonine Protein Kinase, STRAD STe20 Relater ADaptor, T Thymine TNM Tumor Node Metastasis TSA Trichostatin A TSC Tuberous Sclerosis Complex TSG Tumor Supressor Gene UBA Ubiquitin Associated UICC Union for Cancer Control WHO World Health Organization WPWS Wolff-Parkinsin-White syndrome

11 I. Introduction

12 INTRODUCTION 1. Lung Cancer 1.1 Epidemiology of Lung Cancer Incidence Cancer is one of the leading causes of morbidity and mortality worldwide (Peto 2001). According to GLOBOCAN 2012 (Ferlay J 2013), an estimated 14.1 million new cancer cases and 8.2 million cancer-related deaths occurred in 2012, compared with 12.7 million and 7.6 million, respectively, in Prevalence estimates for 2012 show that there were 32.6 million people (over the age of 15 years) alive who had had a cancer diagnosed in the previous five years. The most commonly diagnosed cancers worldwide were those of the lung (1.8 million, 13.0% of the total), breast (1.7 million, 11.9%), and colorectum (1.4 million, 9.7%) Figure 1. Figure 1. The most commonly diagnosted cancers worldwide. Excluding non melanoma skin cancer, 2012 estimates. The data are derived from the IARC GLOBOCAN 2012 database (Ferlay J 2013). Projections based on the GLOBOCAN 2012 (Ferlay J 2013) estimates predict a substantive increase to 19.3 million new cancer cases per year by 2025, due to growth and ageing of the global population. More than half of all cancers (56.8%) and cancer deaths (64.9%) in 2012 occurred in less developed regions of the world, and these proportions will increase further by

13 INTRODUCTION Lung cancer has been estimated as the most common cancer in the world for se veral decades (Figure 2) (Ferlay J 2010), (Parkin, Stjernsward et al. 1984), (Parkin, Laara et al. 1988; Parkin, Pisani et a l ), (Parkin, P isani et a l ), (Parkin, Bray et al ). An estimated 1.61 million people across the world were diagnosed with lung cancer in 2008, accounting for 13% of the total. Figure 2. T rends in the R anking o f New Ca ses of Ca ncer Wo rldwide, The d ata are derived from the IARC GLOBOCAN 2008 database.globocan 2008 (Ferlay J 2010). Lung cancer has a high incidence in both developing countries and areas undergoing economic development such a s China (Parkin 2002 ). Although thes e r egional differences mi ght be explained b y genetic di fferences a mong popula tions, variations in lifestyles, environmental exposures and medical practices such as screening are also likely to be important determinants of cancer risk. This assumption is reinforced b y migration pa tterns that show that incide nce of cancer among mi grants more c losely r eflects the ra tes in the adoptive c ountry. Lung can cer incidence rates are highest in Europe and Northern America and lowest in parts of Africa (Figure 3). More than half (55%) of the cases occurred in the developing world (Ferlay J 2010)

14 INTRODUCTION Figure 3. Incidence of lung cancer. There is substantial global variability in lung cancer incidence (measures as age-standardized rates) occurring in people living in development countries. Lung cancer incidence is currently high in development countries as well as those countries undergoing economic transition us China. (Ferlay J 2013). The disease remains as the most common cancer in men worldwide (1.2 million, 16.7% of the total) with the highest estimated age-standardised incidence rates in Central and Eastern Europe (53.5 per 100,000) and Eastern Asia (50.4 per 100,000). Notably low incidence rates are observed in Middle and Western Africa (2.0 and 1.7 per 100,000 respectively) (Figure 4). In women, the incidence rates are generally lower and the geographical pattern is a little different, mainly reflecting different historical exposure to tobacco smoking. Thus the highest estimated rates are in Northern America (33.8) and Northern Europe (23.7) with a relatively high rate in Eastern Asia (19.2) and the lowest rates again in Western and Middle Africa (1.1 and 0.8 respectively) (Figure 5)

15 INTRODUCTION Figure 4. Incidence / mortality of Lung Cancer in Males by World Regions. (Ferlay J 2013). Figure 5. Incidence / Mortality of Lung Cancer in Females by World Region. (Ferlay J 2013)

16 INTRODUCTION Mortality Deaths from c ancer in the world are pr ojected to continue rising, influe nced in part by an increasing and aging global population. Lung cancer is the most common c ause of de ath from cancer worldwide, e stimated to be responsible for nearly one in five (1.59 million deaths, 19.4% of the total) (Figure 6). Because of its high f atality (the ov erall r atio of mort ality t o incide nce is 0.87) a nd the relative lack of variability in survival in different world regions, the geographical patterns in mortality closely follow those in incidence. Figure 6. The most co mmonly ca uses o f ca ncer death worldwide. Excluding n on m elanoma skin. ca ncer, esti mates. The data are derived f rom th e IARC G LOBOCAN database (Ferlay J 2013). Due to the long time-lag between exposure to lung cancer risk factors, such as smoking, and the onset of the disea se it self, lung cancer incidence a nd morta lity for wo men and m en tends to reflect prior and long-term exposures to risk. Broadly speaking, patterns of lung cancer incidence and mortality show higher rates of the disease among men than women (Figure 4-Figure 5). In the United States of A merica (U SA), fo r example, in 2000 the age-adjusted lung c ancer incidence rate was 79.7 per population for males, compared with a rate of 49.7 per for fe males (SEER 2003 ). Similarly, in the United King dom, the age-standardized lung cancer incidence ra te among male s is approximately twice that in women (70.4 pe r population in men and 34.9 per popul ation in females in 1999) (Cancer.Research.UK - 6 -

17 INTRODUCTION 2003). But in 2012, lung cancer was expected to account for 26% of all female cancer deaths and 29% of all male cancer deaths (American Cancer Society 2012). Lung cancer accounts for more deaths than any other cancer in both men and women. An estimated 160,340 deaths, accounting for about 28% of all cancer deaths, are expected to occur in 2012 (American Cancer Society 2012). Death rates began declining in men in 1991; from 2004 to 2008, rates decreased 2.6% per year. Lung cancer death rates did not begin declining in women until 2003; from 2004 to 2008, rates decreased by 0.9% per year. Gender differences in lung cancer mortality patterns reflect historical differences between men and women in the uptake and reduction of cigarette smoking over the past 50 years (American Cancer Society 2012). 1.2 Lung cancer causes Smoking Lung cancer is unique among human solid cancers in that a single environmental factor-tobacco smoke- is believed to promote sequential changes in target cells that lead to carcinogenesis. The first references on the carcinogenic effect of the tobacco are of more than 200 years ago in the book Cautions against the inmoderate uses of snuff and the book: Chirurgical Observations published on 1775 by the Dr. Percivall Pott. It was not until 1914 that the carcinogenic nature of the contained hydrocarbons was demonstrated in the solid and tarred particles of the tobacco smoke (Yamagawa and Ichikawa 1915). Manufactured cigarettes were introduced at the beginning of the twentieth century. Since then the global consumption of cigarettes has been rising progressively. While consumption is leveling off, and even decreasing in some countries, worldwide more people are smoking and they are smoking more cigarettes. The numbers of smokers will increase mainly due to expansion of the world s population. Pipe and cigar smoking can also cause lung cancer, although the risk is not as high as with cigarette smoking (Wald and Watt 1997).While someone who smokes one pack of cigarettes per - 7 -

18 INTRODUCTION day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking. In Europe the percentage of smokers is about 30%. Overall, ~33% of the adult world population smokes; this equates to 1.1 billion people (of which 200 million are women). The percent of the male population that smokes is 47% while the rate among females is 12%. In developing countries, the percentages are 48% in men and 7% in women, while in the developed countries 42% of the men are smoking and 24% of women (Fuster, O'Rourke et al. 2005). At the moment it is believed that 90% of all the deaths for lung cancer are caused by tobacco. Worldwide, tobacco use causes more than 5 million deaths per year. In total, tobacco use is responsible for the death of about 1 in 10 adults worldwide (WHO 2011). Based on the current trends, the World Health Organization (WHO) predicts that by the year 2020, tobacco will cause in the world more than 10 million deaths a year, (Warren, Jones et al. 2008), causing more deaths than AIDS, tuberculosis, traffic accidents, deaths at birth, suicide and homicides together. Passive smoking The National Cancer Institute s 10th Smoking and Tobacco Control Monograph reviewed studies published between 1991 and 1997 in the United States, Europe, and Asia (Wu 1999). It included studies on environmental tobacco smoke exposure from spouses and the workplace and exposure in other social settings. They concluded that environmental tobacco smoke exposure resulted in an excess risk of 20% for developing lung cancer in the never smokers. Asbestos fibers Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace is a common source of exposure to asbestos fibers, as asbestos was widely used in the past for both thermal and acoustic insulation materials. Lung cancer can occur in nonsmokers exposed to asbestos; however, the risk is magnified several-fold by smoking (Boffetta 2004)

19 INTRODUCTION Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in exposed workers. Workers exposed to asbestos who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers not exposed to asbestos, and those asbestos workers who smoke have a risk that is 50 to 90 times greater than nonsmokers. Environmental and occupational exposures People in developing countries are exposed to broader ranges of occupational and environmental risks, as more people are involved in manufacturing, farming, mining or other industrial occupations than developed countries. Research in China, for instance, has shown a positive association between lung cancer and radon gas exposure (Lubin, Wang et al. 2004), which is high in some homes and among underground miners. Radon gas is a natural, chemically inert gas that is a natural decay product of uranium. An estimated 12% of lung cancer deaths are attributable to radon gas. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. In both China and India, indoor air pollution due to burning of coal and biomass for cooking and heating in homes has also been associated with lung cancer (Kleinerman, Wang et al. 2000; Smith 2000). Air Pollution Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk similar to that of passive smoking for the development of lung cancer. Genetic predisposition While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Genetic variation causes many metabolic differences between individuals, and there is much interest in understanding the potential impact of this variation on susceptibility to cancer and - 9 -

20 INTRODUCTION cancer pathogenesis. Specific mutations in single genes have been reported to greatly increase the risk of some types of cancer, although the prevalence of these mutations is rare at a population level. By contrast, common genetic polymorphisms that contribute only a modest variation in risk can have a greater impact on public health, especially in conjunction with environmental exposures. Lung diseases The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with a slightly increased risk (four to six times the risk of a nonsmoker). Survivors of lung cancer have a greater risk than the general population of developing a second lung cancer. Survivors of non-small cell lung cancers, have an additive risk of 1% -2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs), the risk for development of second cancers approaches 6% per year. Diet So far, much of the diet and cancer research conducted in developing nations has focused on specific diet components. There are many dietary variations, especially among populations in Asia, Africa or Latin America, that might be associated with disease risk (Rastogi, Hildesheim et al. 2004). Turmeric, a yellow-colour spice and flavor commonly consumed by millions of people, particularly in South Asia, has traditionally been used as a remedy for liver ailment. Curcumin, a constituent of turmeric, is a phytochemical that is currently being researched for its anti-tumour properties, such as inducing cell-growth inhibition and apoptosis. Age The population of the world is ageing; this is important because cancer predominantly affects older people. Almost 70% of people diagnosed with the condition are over 65 years of age, while less than 3% of cases occur in people under age

21 INTRODUCTION The median age increased from 23.5 years in 1950 to 26.4 years in By 2050, the median age is projected to reach 37.8 years. The proportion of people in the world aged 60 or older will rise from the current 10% to 22% in 2050 (UnitedNations 1999). There are big variations in the age structures of populations of more developed compared with less developed countries (UnitedNations 1999) (Ferlay J.B.F 2004). Currently 20% of the populations in the more developed regions are aged over 60 compared with 8% in the less developed regions. By 2050 these proportions are expected to rise to 33% and 19% respectively. The countries with the oldest populations in the world include Italy, Japan and Germany and the countries with the youngest include Uganda, Niger and Yemen (UnitedNations 1999). World life expectancy at birth is now at 65 years, having increased by a remarkable 20 years since By 2050, life expectancy is expected to exceed 76 years (UnitedNations 1999). 1.3 Types of Lung Cancer Lung cancers are broken down into two major types, small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC). This classification is based upon the microscopic appearance of the tumor cells themselves. These two types of cancers grow and spread in different ways, so a distinction between these two types is important SCLC Small cell lung cancers comprise approximately 20-25% of all lung cancer cases. SCLC is strongly related to cigarette smoking, with only 1% of these tumors occurring in nonsmokers. This type of lung cancer originates in an inner layer of the walls of the bronchi called the bronchial submucosa, and grows aggressively (in comparison with non small cell lung cancers), quickly spreading into surrounding tissues, and ultimately, through the body. Symptoms are generally not noticeable until the cancer has spread into other parts of the body. Because of their rapid growth pace and tendency to metastasize, small cell cancers are described with only two stages, limited when spread is contained to the localized area of the lung and immediate surrounding tissues, and extensive when the cancer has spread throughout the body

22 INTRODUCTION Referring to a specific cell type often seen in SCLC, these cancers are sometimes called oat cell carcinomas NSCLC NSCLC are the most common lung cancers, accounting for about 80% of all lung cancers. NSCLC can be divided into three main types that are named based upon the type of cells found in the tumor: Adenocarcinomas are the most commonly seen type of NSCLC. While adenocarcinomas are associated with smoking like other lung cancers, this type is especially observed as well in nonsmokers who develop lung cancer. Most adenocarcinomas arise in the outer, or peripheral, areas of the lungs. The most frequents subtypes are: acinar adenocarcinoma, papillary adenocarcinoma, micropapillary and solid (Travis, Brambilla et al. 2011). Squamous cell carcinomas were formerly more common than adenocarcinomas; at present, they account for about 30% of NSCLC. Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Also known as epidermoid carcinomas, squamous cell cancers arise most frequently in the central chest area in the bronchi. Large cell lung cancer sometimes referred to as undifferentiated carcinomas, are the least common type of NSCLC. 1.4 Stage of lung cancer Stages of Small Cell Lung Cancer The objectives of staging in SCLC are to identify localized disease, for which radiation therapy may be suitable, and to quantify the extent of the disease before therapy. Small cell lung cancer is typically classified according to the 2-stage system development by the Veterans Administration Lung Cancer Study Group: Limited stage: when spread is contained to the localized area of the lung and immediate surrounding tissues. Extensive stage: cancer is found in tissues of the chest outside of the lung in which it began or cancer is found in distant organs, therefore when the cancer has spread throughout the body

23 INTRODUCTION Stages of Non-Small Cell Lung Cancer The International Staging System for Lung Cancer has provided a common language for communication about patients with this disease, and the scientific community has been served well by its application. This system classifies the extent of disease based mostly on anatomic information on the extent of the primary tumor, regional lymph nodes, and distant metastases. This classification was developed in the 1940s by Pierre Denoix PF of France and formalized by the Union for Cancer Control (UICC) in the 1950s with the formation of the Committee on Clinical Stage Classification and Applied Statistics. The American Joint Committee on Cancer (AJCC) was founded in 1959 to complete this work. The classification of malignant tumors is according to tumor-node-metastasis (TNM) that describes the extent of a person s cancer. But the concept of stage grouping came later ((UICC) 1988). The TNM system is based on 3 key pieces of information T describes the size of the original (primary) tumor and whether it has grown into nearby areas. N describes the spread of cancer to nearby (regional) lymph nodes that are involved. M describes distant metastasis (spread of cancer from one part of the body to another). Revisions in stage grouping of the TNM subsets in the schema of the International System for Staging Lung Cancer were made to provide greater specificity for identified patient with similar prognoses and treatment options (Table1-Table2). The rules of classification and staging correspond to those appearing in the seventh edition of the AJCC Cancer Staging Manual 2009 and have approval of all national TNM committees

CHAPTER 2: UNDERSTANDING CANCER

CHAPTER 2: UNDERSTANDING CANCER CHAPTER 2: UNDERSTANDING CANCER INTRODUCTION We are witnessing an era of great discovery in the field of cancer research. New insights into the causes and development of cancer are emerging. These discoveries

More information

DNA METHYLATION AND THE CONCEPT OF EPIGENETICS

DNA METHYLATION AND THE CONCEPT OF EPIGENETICS DNA METHYLATION AND THE CONCEPT OF EPIGENETICS The term Epigenetics describes heritable genetic modifications that are not attributable to changes in the primary DNA sequence. Epigenetic modifications

More information

Psychoonkology, Sept. 2010 lifestyle factors and epigenetics

Psychoonkology, Sept. 2010 lifestyle factors and epigenetics Psychoonkology, Sept. 2010 lifestyle factors and epigenetics Alexander G. Haslberger Dep. für Ernährungswissenschaften Univ. of Vienna Working group: Food, GI-Microbiology, Epigenetics Content Health:

More information

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function:

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function: Cancer is a genetic disease: Inherited cancer Sporadic cancer What is Cancer? Cancer typically involves a change in gene expression/function: Qualitative change Quantitative change Any cancer causing genetic

More information

Lung cancer. A guide for journalists on Non-Small Cell Lung Cancer (NSCLC) and its treatment

Lung cancer. A guide for journalists on Non-Small Cell Lung Cancer (NSCLC) and its treatment Lung cancer A guide for journalists on Non-Small Cell Lung Cancer (NSCLC) and its treatment Contents Contents 2 3 Section 1: Lung Cancer 4 i. Types of lung cancer 4 ii. Causes and risk factors 5 iii. Symptoms

More information

Lung Cancer: Diagnosis, Staging and Treatment

Lung Cancer: Diagnosis, Staging and Treatment PATIENT EDUCATION patienteducation.osumc.edu Lung Cancer: Diagnosis, Staging and Treatment Cancer begins in our cells. Cells are the building blocks of our tissues. Tissues make up the organs of the body.

More information

Lung Cancer: Diagnosis, Staging and Treatment

Lung Cancer: Diagnosis, Staging and Treatment PATIENT EDUCATION patienteducation.osumc.edu Lung Cancer: Diagnosis, Staging and Treatment Cancer starts in our cells. Cells are the building blocks of our tissues. Tissues make up the organs of the body.

More information

Lung cancer is not just one disease. There are two main types of lung cancer:

Lung cancer is not just one disease. There are two main types of lung cancer: 1. What is lung cancer? 2. How common is lung cancer? 3. What are the risk factors for lung cancer? 4. What are the signs and symptoms of lung cancer? 5. How is lung cancer diagnosed? 6. What are the available

More information

Analysis of the DNA Methylation Patterns at the BRCA1 CpG Island

Analysis of the DNA Methylation Patterns at the BRCA1 CpG Island Analysis of the DNA Methylation Patterns at the BRCA1 CpG Island Frédérique Magdinier 1 and Robert Dante 2 1 Laboratory of Molecular Biology of the Cell, Ecole Normale Superieure, Lyon, France 2 Laboratory

More information

Lung Cancer. This reference summary will help you better understand lung cancer and the treatment options that are available.

Lung Cancer. This reference summary will help you better understand lung cancer and the treatment options that are available. Lung Cancer Introduction Lung cancer is the number one cancer killer of men and women. Over 165,000 people die of lung cancer every year in the United States. Most cases of lung cancer are related to cigarette

More information

Male. Female. Death rates from lung cancer in USA

Male. Female. Death rates from lung cancer in USA Male Female Death rates from lung cancer in USA Smoking represents an interesting combination of an entrenched industry and a clearly drug-induced cancer Tobacco Use in the US, 1900-2000 5000 100 Per Capita

More information

MUTATION, DNA REPAIR AND CANCER

MUTATION, DNA REPAIR AND CANCER MUTATION, DNA REPAIR AND CANCER 1 Mutation A heritable change in the genetic material Essential to the continuity of life Source of variation for natural selection New mutations are more likely to be harmful

More information

Epidemiology, Staging and Treatment of Lung Cancer. Mark A. Socinski, MD

Epidemiology, Staging and Treatment of Lung Cancer. Mark A. Socinski, MD Epidemiology, Staging and Treatment of Lung Cancer Mark A. Socinski, MD Associate Professor of Medicine Multidisciplinary Thoracic Oncology Program Lineberger Comprehensive Cancer Center University of

More information

Biological Sciences Initiative. Human Genome

Biological Sciences Initiative. Human Genome Biological Sciences Initiative HHMI Human Genome Introduction In 2000, researchers from around the world published a draft sequence of the entire genome. 20 labs from 6 countries worked on the sequence.

More information

Primary -Benign - Malignant Secondary

Primary -Benign - Malignant Secondary TUMOURS OF THE LUNG Primary -Benign - Malignant Secondary The incidence of lung cancer has been increasing almost logarithmically and is now reaching epidemic levels. The overall cure rate is very low

More information

How Cancer Begins???????? Chithra Manikandan Nov 2009

How Cancer Begins???????? Chithra Manikandan Nov 2009 Cancer Cancer is one of the most common diseases in the developed world: 1 in 4 deaths are due to cancer 1 in 17 deaths are due to lung cancer Lung cancer is the most common cancer in men Breast cancer

More information

Department of BioScience Technology Chung Yuan Christian University 2015/08/13

Department of BioScience Technology Chung Yuan Christian University 2015/08/13 Department of BioScience Technology Chung Yuan Christian University 2015/08/13 Cancer Cells Cancer, the 1st leading cause of death, is an example of a disease that arises from abnormalities in cell function

More information

Pathology of lung cancer

Pathology of lung cancer Pathology of lung cancer EASO COURSE ON LUNG CANCER AND MESOTHELIOMA DAMASCUS (SYRIA), MAY 3-4, 2007 Gérard ABADJIAN MD Pathologist Associate Professor, Saint Joseph University Pathology Dept. Hôtel-Dieu

More information

The following information is only meant for people who have been diagnosed with advanced non-small cell

The following information is only meant for people who have been diagnosed with advanced non-small cell Important information for people with advanced non-small cell lung cancer The following information is only meant for people who have been diagnosed with advanced non-small cell lung cancer (NSCLC). NSCLC

More information

Control of Gene Expression

Control of Gene Expression Home Gene Regulation Is Necessary? Control of Gene Expression By switching genes off when they are not needed, cells can prevent resources from being wasted. There should be natural selection favoring

More information

Gene mutation and molecular medicine Chapter 15

Gene mutation and molecular medicine Chapter 15 Gene mutation and molecular medicine Chapter 15 Lecture Objectives What Are Mutations? How Are DNA Molecules and Mutations Analyzed? How Do Defective Proteins Lead to Diseases? What DNA Changes Lead to

More information

About lung cancer. Contents. The lungs

About lung cancer. Contents. The lungs This information is an extract from the booklet Understanding lung cancer. You may find the full booklet helpful. We can send you a free copy see page 7. The lungs Contents The lungs Types of lung cancer

More information

Disease/Illness GUIDE TO ASBESTOS LUNG CANCER. What Is Asbestos Lung Cancer? www.simpsonmillar.co.uk Telephone 0844 858 3200

Disease/Illness GUIDE TO ASBESTOS LUNG CANCER. What Is Asbestos Lung Cancer? www.simpsonmillar.co.uk Telephone 0844 858 3200 GUIDE TO ASBESTOS LUNG CANCER What Is Asbestos Lung Cancer? Like tobacco smoking, exposure to asbestos can result in the development of lung cancer. Similarly, the risk of developing asbestos induced lung

More information

MOLECULAR BIOLOGY OVERVIEW NUCLEIC ACIDS: THE BASICS

MOLECULAR BIOLOGY OVERVIEW NUCLEIC ACIDS: THE BASICS MOLECULAR BIOLOGY OVERVIEW NUCLEIC ACIDS: THE BASICS Richard L. Hodinka, Ph.D. University of South Carolina School of Medicine Greenville Greenville Health System, Greenville, SC hodinka@greenvillemed.sc.edu

More information

Genetic information (DNA) determines structure of proteins DNA RNA proteins cell structure 3.11 3.15 enzymes control cell chemistry ( metabolism )

Genetic information (DNA) determines structure of proteins DNA RNA proteins cell structure 3.11 3.15 enzymes control cell chemistry ( metabolism ) Biology 1406 Exam 3 Notes Structure of DNA Ch. 10 Genetic information (DNA) determines structure of proteins DNA RNA proteins cell structure 3.11 3.15 enzymes control cell chemistry ( metabolism ) Proteins

More information

بسم هللا الرحمن الرحيم

بسم هللا الرحمن الرحيم بسم هللا الرحمن الرحيم Updates in Mesothelioma By Samieh Amer, MD Professor of Cardiothoracic Surgery Faculty of Medicine, Cairo University History Wagner and his colleagues (1960) 33 cases of mesothelioma

More information

TNM staging and prognosis. Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania

TNM staging and prognosis. Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania TNM staging and prognosis Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania The Basics of TNM Staging Premises: Cancers of the same

More information

Abnormalities of Chromosome Structure

Abnormalities of Chromosome Structure Abnormalities of Chromosome Structure Structural rearrangements result from chromosome breakage, followed by reconstitution in an abnormal combination. Whereas rearrangements can take place in many ways,

More information

Regulation of Gene Expression

Regulation of Gene Expression Chapter 18 Regulation of Gene Expression PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from

More information

Anatomy of the Lung: The Role it Plays in Staging

Anatomy of the Lung: The Role it Plays in Staging Anatomy of the Lung: The Role it Plays in Staging Kirk D. Jones, MD UCSF Dept. of Pathology kirk.jones@ucsf.edu College of American Pathologists, Cancer Committee Member Overview Historical notes on staging

More information

GENE REGULATION. Teacher Packet

GENE REGULATION. Teacher Packet AP * BIOLOGY GENE REGULATION Teacher Packet AP* is a trademark of the College Entrance Examination Board. The College Entrance Examination Board was not involved in the production of this material. Pictures

More information

Complex multicellular organisms are produced by cells that switch genes on and off during development.

Complex multicellular organisms are produced by cells that switch genes on and off during development. Home Control of Gene Expression Gene Regulation Is Necessary? By switching genes off when they are not needed, cells can prevent resources from being wasted. There should be natural selection favoring

More information

STANDARD 2 Students will demonstrate appropriate safety procedures and equipment use in the laboratory.

STANDARD 2 Students will demonstrate appropriate safety procedures and equipment use in the laboratory. BIOTECHNOLOGY Levels: 11-12 Units of Credit: 1.0 CIP Code: 51.1201 Prerequisite: Biology or Chemistry Skill Certificates: #708 COURSE DESCRIPTION is an exploratory course designed to create an awareness

More information

Understanding Your Surgical Options for Lung Cancer

Understanding Your Surgical Options for Lung Cancer Information Booklet for Patients Understanding Your Surgical Options for Lung Cancer Understanding Lung Cancer If you have just been diagnosed with lung cancer, this booklet will serve as an informational

More information

Benefits in oncology. Mechanism of action

Benefits in oncology. Mechanism of action Mechanism of action The word cancer refers to a number of different diseases that share a common trait: the rapid, unrestrained growth and spread of cells that can invade and destroy surrounding tissues,

More information

OCCUPATIONAL LUNG CANCER

OCCUPATIONAL LUNG CANCER OCCUPATIONAL LUNG CANCER Anwar Jusuf, Agus Dwi Susanto Department of Pulmonology & Respiratory Medicine, Faculty of Medicine University Of Indonesia - Persahabatan Hospital-Jakarta INTRODUCTION Occupational

More information

Neoplasms. Review of Normal Cells. Bio 375 Pathophysiology

Neoplasms. Review of Normal Cells. Bio 375 Pathophysiology Neoplasms Bio 375 Pathophysiology Review of Normal Cells During its life span, each cell follows the basic cell cycle of growth and reproduction called mitosis The timing of each event varies with the

More information

Evolution of Staging in Lung Cancer

Evolution of Staging in Lung Cancer AATS Annual Meeting, Toronto, 2014. General Thoracic Session. Evolution of Staging in Lung Cancer Peter Goldstraw, Honorary Consultant Thoracic Surgeon, Royal Brompton Hospital, Emeritus Professor of Thoracic

More information

General Information About Non-Small Cell Lung Cancer

General Information About Non-Small Cell Lung Cancer General Information About Non-Small Cell Lung Cancer Non-small cell lung cancer is a disease in which malignant (cancer) cells form in the tissues of the lung. The lungs are a pair of cone-shaped breathing

More information

Nuevas tecnologías basadas en biomarcadores para oncología

Nuevas tecnologías basadas en biomarcadores para oncología Nuevas tecnologías basadas en biomarcadores para oncología Simposio ASEBIO 14 de marzo 2013, PCB Jose Jimeno, MD, PhD Co-Founder / Vice Chairman Pangaea Biotech SL Barcelona, Spain PANGAEA BIOTECH BUSINESS

More information

BINF6201/8201. Basics of Molecular Biology

BINF6201/8201. Basics of Molecular Biology BINF6201/8201 Basics of Molecular Biology 08-26-2016 Linear structure of nucleic acids Ø Nucleic acids are polymers of nucleotides Ø Nucleic acids Deoxyribonucleic acids (DNA) Ribonucleic acids (RNA) Phosphate

More information

Fact Sheet 14 EPIGENETICS

Fact Sheet 14 EPIGENETICS This fact sheet describes epigenetics which refers to factors that can influence the way our genes are expressed in the cells of our body. In summary Epigenetics is a phenomenon that affects the way cells

More information

Breast Cancer. The Pathology report gives an outline on direction of treatment. It tells multiple stories to help us understand the patient s cancer.

Breast Cancer. The Pathology report gives an outline on direction of treatment. It tells multiple stories to help us understand the patient s cancer. Breast Cancer What Does the Pathology Report Say Normal Cells The Pathology report gives an outline on direction of treatment. It tells multiple stories to help us understand the patient s cancer. Non-Invasive

More information

Ch. 12: DNA and RNA 12.1 DNA Chromosomes and DNA Replication

Ch. 12: DNA and RNA 12.1 DNA Chromosomes and DNA Replication Ch. 12: DNA and RNA 12.1 DNA A. To understand genetics, biologists had to learn the chemical makeup of the gene Genes are made of DNA DNA stores and transmits the genetic information from one generation

More information

CD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy

CD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy CD22 Antigen Is Broadly Expressed on Lung Cancer Cells and Is a Target for Antibody-Based Therapy Joseph M. Tuscano, Jason Kato, David Pearson, Chengyi Xiong, Laura Newell, Yunpeng Ma, David R. Gandara,

More information

Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources

Just the Facts: A Basic Introduction to the Science Underlying NCBI Resources 1 of 8 11/7/2004 11:00 AM National Center for Biotechnology Information About NCBI NCBI at a Glance A Science Primer Human Genome Resources Model Organisms Guide Outreach and Education Databases and Tools

More information

Epigenetic mechanisms regulate the interpretation of genetic information. Frank Lyko Epigenetics

Epigenetic mechanisms regulate the interpretation of genetic information. Frank Lyko Epigenetics Epigenetic mechanisms regulate the interpretation of genetic information 7/19/2011 Seite 1 DNA methylation is a central epigenetic mechanism NH 2 NH 2 N Dnmt N CH 3 O N O N 4% of genomic C is methylated

More information

Chapter 12 - DNA Technology

Chapter 12 - DNA Technology Bio 100 DNA Technology 1 Chapter 12 - DNA Technology Among bacteria, there are 3 mechanisms for transferring genes from one cell to another cell: transformation, transduction, and conjugation 1. Transformation

More information

Structure and Function of DNA

Structure and Function of DNA Structure and Function of DNA DNA and RNA Structure DNA and RNA are nucleic acids. They consist of chemical units called nucleotides. The nucleotides are joined by a sugar-phosphate backbone. The four

More information

The Human Genome Project. From genome to health From human genome to other genomes and to gene function Structural Genomics initiative

The Human Genome Project. From genome to health From human genome to other genomes and to gene function Structural Genomics initiative The Human Genome Project From genome to health From human genome to other genomes and to gene function Structural Genomics initiative June 2000 What is the Human Genome Project? U.S. govt. project coordinated

More information

AP Biology Review Packet 4: Viruses, Bacteria and Expression & DNA Technology

AP Biology Review Packet 4: Viruses, Bacteria and Expression & DNA Technology AP Biology Review Packet 4: Viruses, Bacteria and Expression & DNA Technology 3A1- DNA, and in some cases RNA, is the primary source of heritable information. 3B1- Gene Regulation results in differential

More information

Life. In nature, we find living things and non living things. Living things can move, reproduce, as opposed to non living things.

Life. In nature, we find living things and non living things. Living things can move, reproduce, as opposed to non living things. Computat onal Biology Lecture 1 Life In nature, we find living things and non living things. Living things can move, reproduce, as opposed to non living things. Both are composed of the same atoms and

More information

Epithelial Ovarian Cancer

Epithelial Ovarian Cancer Epithelial Ovarian Cancer Fred Ueland, MD University of Kentucky Gynecologic Oncology Risk Factors Incessant ovulation Early menarche, late menopause, low parity Family history Acquired genetic mutations

More information

An Overview of Lung Cancer Symptoms, Pathophysiology, And Treatment Linda H. Yoder

An Overview of Lung Cancer Symptoms, Pathophysiology, And Treatment Linda H. Yoder CE Objectives and Evaluation Form appear on page 235. An Overview of Lung Cancer Symptoms, Pathophysiology, And Treatment Linda H. Yoder Patients with lung cancer can provide treatment challenges for even

More information

Contents. molecular biology techniques. - Mutations in Factor II. - Mutations in MTHFR gene. - Breast cencer genes. - p53 and breast cancer

Contents. molecular biology techniques. - Mutations in Factor II. - Mutations in MTHFR gene. - Breast cencer genes. - p53 and breast cancer Contents Introduction: biology and medicine, two separated compartments What we need to know: - boring basics in DNA/RNA structure and overview of particular aspects of molecular biology techniques - How

More information

Forensic DNA Testing Terminology

Forensic DNA Testing Terminology Forensic DNA Testing Terminology ABI 310 Genetic Analyzer a capillary electrophoresis instrument used by forensic DNA laboratories to separate short tandem repeat (STR) loci on the basis of their size.

More information

9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH

9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH 9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH Differentiated thyroid cancer expresses the TSH receptor on the cell membrane and responds to TSH stimulation by increasing

More information

ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials)

ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials) ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials) 3 Integrated Trials Testing Targeted Therapy in Early Stage Lung Cancer Part of NCI s Precision Medicine Effort in

More information

Cancer SBL101. James Gomes School of Biological Sciences Indian Institute of Technology Delhi

Cancer SBL101. James Gomes School of Biological Sciences Indian Institute of Technology Delhi Cancer SBL101 James Gomes School of Biological Sciences Indian Institute of Technology Delhi All Figures in this Lecture are taken from 1. Molecular biology of the cell / Bruce Alberts et al., 5th ed.

More information

From DNA to Protein. Chapter 14

From DNA to Protein. Chapter 14 From DNA to Protein Chapter 14 Impacts, Issues: Ricin and your Ribosomes Ricin is toxic because it inactivates ribosomes, the organelles which assemble amino acids into proteins, critical to life processes

More information

Breast cancer. A guide for journalists on breast cancer and its treatment

Breast cancer. A guide for journalists on breast cancer and its treatment Breast cancer A guide for journalists on breast cancer and its treatment Contents Contents 2 3 Section 1: Breast Cancer 4 i. What is breast cancer? 4 ii. Types of breast cancer 4 iii. Causes and risk factors

More information

DNA Fingerprinting. Unless they are identical twins, individuals have unique DNA

DNA Fingerprinting. Unless they are identical twins, individuals have unique DNA DNA Fingerprinting Unless they are identical twins, individuals have unique DNA DNA fingerprinting The name used for the unambiguous identifying technique that takes advantage of differences in DNA sequence

More information

Lung Cancer: Practical Application of Imaging In Determining Resectability. Jeremy J. Erasmus, M. D.

Lung Cancer: Practical Application of Imaging In Determining Resectability. Jeremy J. Erasmus, M. D. Lung Cancer: Practical Application of Imaging In Determining Resectability Jeremy J. Erasmus, M. D. 62 year old man with a superior sulcus tumor. Which of the following precludes surgical resection in

More information

Understanding the immune response to bacterial infections

Understanding the immune response to bacterial infections Understanding the immune response to bacterial infections A Ph.D. (SCIENCE) DISSERTATION SUBMITTED TO JADAVPUR UNIVERSITY SUSHIL KUMAR PATHAK DEPARTMENT OF CHEMISTRY BOSE INSTITUTE 2008 CONTENTS Page SUMMARY

More information

B. Dingle MD, FRCPC, Brian Yaremko MD,FRCPC, R. Ash, MD, FRCPC, P. Truong, MD, FRCPC

B. Dingle MD, FRCPC, Brian Yaremko MD,FRCPC, R. Ash, MD, FRCPC, P. Truong, MD, FRCPC Lung Cancer B. Dingle MD, FRCPC, Brian Yaremko MD,FRCPC, R. Ash, MD, FRCPC, P. Truong, MD, FRCPC EPIDEMIOLOGY The estimated incidence of lung cancer in Canada for 2007 is 23,300 with 12,400 occurring in

More information

Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs)

Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs) Lecture 6: Single nucleotide polymorphisms (SNPs) and Restriction Fragment Length Polymorphisms (RFLPs) Single nucleotide polymorphisms or SNPs (pronounced "snips") are DNA sequence variations that occur

More information

NHS Barking and Dagenham Briefing on disease linked to Asbestos in Barking & Dagenham

NHS Barking and Dagenham Briefing on disease linked to Asbestos in Barking & Dagenham APPENDIX 1 NHS Barking and Dagenham Briefing on disease linked to Asbestos in Barking & Dagenham 1. Background 1.1. Asbestos Asbestos is a general name given to several naturally occurring fibrous minerals

More information

Genetics Module B, Anchor 3

Genetics Module B, Anchor 3 Genetics Module B, Anchor 3 Key Concepts: - An individual s characteristics are determines by factors that are passed from one parental generation to the next. - During gamete formation, the alleles for

More information

How many of you have checked out the web site on protein-dna interactions?

How many of you have checked out the web site on protein-dna interactions? How many of you have checked out the web site on protein-dna interactions? Example of an approximately 40,000 probe spotted oligo microarray with enlarged inset to show detail. Find and be ready to discuss

More information

Control of Gene Expression

Control of Gene Expression Control of Gene Expression (Learning Objectives) Explain the role of gene expression is differentiation of function of cells which leads to the emergence of different tissues, organs, and organ systems

More information

Controls Over Genes. Chapter 15

Controls Over Genes. Chapter 15 Controls Over Genes Chapter 15 Impacts, Issues: Between You and Eternity Mutations in some genes predispose individuals to develop certain kinds of cancer; mutations in BRAC genes cause breast cancer normal

More information

Test Your Breast Cancer Knowledge

Test Your Breast Cancer Knowledge Test Your Breast Cancer Knowledge Regular exams and a good understanding can help defend against breast cancer, yet many women hold outdated ideas about their own breast cancer risk. Take this quiz to

More information

micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved

micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved microrna 2 micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved Regulate gene expression by binding complementary regions at 3 regions of target mrnas Act as negative

More information

Mitochondrial DNA Analysis

Mitochondrial DNA Analysis Mitochondrial DNA Analysis Lineage Markers Lineage markers are passed down from generation to generation without changing Except for rare mutation events They can help determine the lineage (family tree)

More information

Ingenious Genes Curriculum Links for AQA AS (7401) and A-Level Biology (7402)

Ingenious Genes Curriculum Links for AQA AS (7401) and A-Level Biology (7402) Ingenious Genes Curriculum Links for AQA AS (7401) and A-Level Biology (7402) 3.1.1 Monomers and Polymers 3.1.4 Proteins 3.1.5 Nucleic acids are important information-carrying molecules 3.2.1 Cell structure

More information

MOLECULAR GENETICS GENETIC ENGINEERING RECOMBINANT DNA. Molecular Genetics Activity #6 page 1

MOLECULAR GENETICS GENETIC ENGINEERING RECOMBINANT DNA. Molecular Genetics Activity #6 page 1 AP BIOLOGY MOLECULAR GENETICS ACTIVITY #6 NAME DATE HOUR RECOMBINANT DNA GENETIC ENGINEERING Molecular Genetics Activity #6 page 1 GENETIC ENGINEERING Molecular Genetics Activity #6 page 2 PART I: PRODUCING

More information

3. The most common form of severely affected people who are having more than 1000 repeats of the CTG triplet are called

3. The most common form of severely affected people who are having more than 1000 repeats of the CTG triplet are called MCQ. Genetics with answers Q1) Choose the best answer for the following questions: 1. What are the repeating units of nucleic acids? A. phosphate molecules B. nucleotides C. bases D. sugar molecules 2.

More information

Human Mendelian Disorders. Genetic Technology. What is Genetics? Genes are DNA 9/3/2008. Multifactorial Disorders

Human Mendelian Disorders. Genetic Technology. What is Genetics? Genes are DNA 9/3/2008. Multifactorial Disorders Human genetics: Why? Human Genetics Introduction Determine genotypic basis of variant phenotypes to facilitate: Understanding biological basis of human genetic diversity Prenatal diagnosis Predictive testing

More information

Fact Sheet 1 AN INTRODUCTION TO DNA, GENES AND CHROMOSOMES

Fact Sheet 1 AN INTRODUCTION TO DNA, GENES AND CHROMOSOMES 10:23 AM11111 DNA contains the instructions for growth and development in humans and all living things. Our DNA is packaged into chromosomes that contain all of our genes. In summary DNA stands for (DeoxyriboNucleic

More information

New strategies in anticancer therapy

New strategies in anticancer therapy 癌 症 診 療 指 引 簡 介 及 臨 床 應 用 New strategies in anticancer therapy 中 山 醫 學 大 學 附 設 醫 院 腫 瘤 內 科 蔡 明 宏 醫 師 2014/3/29 Anti-Cancer Therapy Surgical Treatment Radiotherapy Chemotherapy Target Therapy Supportive

More information

Control of Gene Expression

Control of Gene Expression Control of Gene Expression What is Gene Expression? Gene expression is the process by which informa9on from a gene is used in the synthesis of a func9onal gene product. What is Gene Expression? Figure

More information

The vast majority of RNA functions are concerned with protein synthesis.

The vast majority of RNA functions are concerned with protein synthesis. RNA Structure, Function, and Synthesis RNA RNA differs from DNA in both structural and functional respects. RNA has two major structural differences: each of the ribose rings contains a 2 -hydroxyl, and

More information

Table 24a Thyroid Cancer Average Annual Number of Cancer Cases and Age-Adjusted Incidence Rates* for

Table 24a Thyroid Cancer Average Annual Number of Cancer Cases and Age-Adjusted Incidence Rates* for Thyroid Cancer Figure 24 Definition: Thyroid cancer starts in the thyroid gland. 1 The thyroid is made up of two main types of cells, thyroid follicular cells and parafollicular cells. 1 Different types

More information

Name Date Period. 2. When a molecule of double-stranded DNA undergoes replication, it results in

Name Date Period. 2. When a molecule of double-stranded DNA undergoes replication, it results in DNA, RNA, Protein Synthesis Keystone 1. During the process shown above, the two strands of one DNA molecule are unwound. Then, DNA polymerases add complementary nucleotides to each strand which results

More information

CHAPTER 4: LUNG CANCER DIAGNOSIS AND STAGING

CHAPTER 4: LUNG CANCER DIAGNOSIS AND STAGING CHAPTER 4: LUNG CANCER DIAGNOSIS AND STAGING INTRODUCTION The lungs are vital organs. Working with the heart and circulatory system, they provide lifesustaining oxygen and rid the body of carbon dioxide.

More information

Chapter 18 Regulation of Gene Expression

Chapter 18 Regulation of Gene Expression Chapter 18 Regulation of Gene Expression 18.1. Gene Regulation Is Necessary By switching genes off when they are not needed, cells can prevent resources from being wasted. There should be natural selection

More information

Mesothelioma: Questions and Answers

Mesothelioma: Questions and Answers CANCER FACTS N a t i o n a l C a n c e r I n s t i t u t e N a t i o n a l I n s t i t u t e s o f H e a l t h D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s Mesothelioma: Questions

More information

Cancer Staging. Introduction. Overview

Cancer Staging. Introduction. Overview Many Hearts Many Minds One Goal Volume 2 Number 3 May 2005 Cancer Staging bt Maureen MacIntyre, Director, Surveillance and Epidemiology Unit, Cancer Care Nova Scotia and Dr. Eva Grunfeld, Clinician Scientist

More information

Lung cancer and asbestos

Lung cancer and asbestos Lung cancer and asbestos Bureau Veritas Training Bill Sanderson For the benefit of business and people To begin with.. There are known knowns, that is there are things we know that we know. There are known

More information

Transcript for Asbestos Information for the Community

Transcript for Asbestos Information for the Community Welcome to the lecture on asbestos and its health effects for the community. My name is Dr. Vik Kapil and I come to you from the Centers for Disease Control and Prevention, Agency for Toxic Substances

More information

Gestational Trophoblastic Tumors

Gestational Trophoblastic Tumors 32 Gestational Trophoblastic Tumors C58.9 Placenta SUMMARY OF CHANGES Gestational trophoblastic tumors are effectively treated with chemotherapy even when widely metastatic so that traditional anatomic

More information

Mesothelioma. 1995-2013, The Patient Education Institute, Inc. www.x-plain.com ocft0101 Last reviewed: 03/21/2013 1

Mesothelioma. 1995-2013, The Patient Education Institute, Inc. www.x-plain.com ocft0101 Last reviewed: 03/21/2013 1 Mesothelioma Introduction Mesothelioma is a type of cancer. It starts in the tissue that lines your lungs, stomach, heart, and other organs. This tissue is called mesothelium. Most people who get this

More information

Systems Biology: A Personal View XV. Network Medicine. Sitabhra Sinha IMSc Chennai

Systems Biology: A Personal View XV. Network Medicine. Sitabhra Sinha IMSc Chennai Systems Biology: A Personal View XV. Network Medicine Sitabhra Sinha IMSc Chennai Diseases, Genes and Networks http://learn.genetics.utah.edu/ Now that we have the ability to sequence entire genomes, can

More information

2. True or False? The sequence of nucleotides in the human genome is 90.9% identical from one person to the next. False (it s 99.

2. True or False? The sequence of nucleotides in the human genome is 90.9% identical from one person to the next. False (it s 99. 1. True or False? A typical chromosome can contain several hundred to several thousand genes, arranged in linear order along the DNA molecule present in the chromosome. True 2. True or False? The sequence

More information

Chapter 2. Introduction to some basic features of genetic information: From DNA to proteins

Chapter 2. Introduction to some basic features of genetic information: From DNA to proteins Chapter 2 Introduction to some basic features of genetic information: From DNA to proteins DAVID QUIST, 1 KAARE M. NIELSEN 1, 2 AND TERJE TRAAVIK 1, 3 1 THE NORWEGIAN INSTITUTE OF GENE ECOLOGY (GENØK),

More information

Molecular Biology of The Cell - An Introduction

Molecular Biology of The Cell - An Introduction Molecular Biology of The Cell - An Introduction Nguyen Phuong Thao School of Biotechnology International University Contents Three Domain of Life The Cell Eukaryotic Cell Prokaryotic Cell The Genome The

More information

RNA and Protein Synthesis

RNA and Protein Synthesis Name lass Date RN and Protein Synthesis Information and Heredity Q: How does information fl ow from DN to RN to direct the synthesis of proteins? 13.1 What is RN? WHT I KNOW SMPLE NSWER: RN is a nucleic

More information

School of Nursing. Presented by Yvette Conley, PhD

School of Nursing. Presented by Yvette Conley, PhD Presented by Yvette Conley, PhD What we will cover during this webcast: Briefly discuss the approaches introduced in the paper: Genome Sequencing Genome Wide Association Studies Epigenomics Gene Expression

More information

Appendix C DNA Replication & Mitosis

Appendix C DNA Replication & Mitosis K.Muma Bio 6 Appendix C DNA Replication & Mitosis Study Objectives: Appendix C: DNA replication and Mitosis 1. Describe the structure of DNA and where it is found. 2. Explain complimentary base pairing:

More information

Lesson Overview. Fermentation. Lesson Overview 13.1 RNA

Lesson Overview. Fermentation. Lesson Overview 13.1 RNA Lesson Overview 13.1 RNA Similarities between DNA & RNA They are both nucleic acids They both have: a 5-carbon sugar, a phosphate group, a nitrogenous base. Comparing RNA and DNA There are three important

More information